Methods and Systems for Submucosal Implantation of a Device for Diagnosis and Treatment with a Therapeutic Agent

ABSTRACT

Instruments, systems, implants, and methods are provided for performing submucosal medical procedures in a desired area of the digestive tract using endoscopy. Instruments include a safe access needle injection instrument, a submucosal tunneling instrument, a submucosal dissection instrument, and a mucosal resection device. A submucosal implant device for diagnosing and treating disorders of the body may be implanted. A passive submucosal implant device may take the form of a drug delivery depot in which a therapeutic agent within the depot elutes from the depot according to a predetermined elution profile. An active submucosal implant device may take the form of a drug delivery device that incorporates a self-contained diagnostic system to determine the appropriate delivery time and dosage of a therapeutic agent to be administered.

FIELD OF THE INVENTION

The present invention relates to a safe access needle injectioninstrument, a submucosal tunneling instrument, a submucosal dissectioninstrument, a submucosal implant device a system and a method forperforming submucosal medical procedures in a desired area of thedigestive tract using an endoscope. One aspect in particular relates tothe implantation of a device in the submucosal layer of the digestivetract for diagnosing or treating disorders of the body.

BACKGROUND OF THE INVENTION

The field of gastrointestinal endoscopy has for many years focused ondiagnostic and therapeutic techniques to observe, modify and removetissues located in the digestive tract. General endoscopic proceduraltechniques such as visualizing, dilating, cutting and manipulatingtissue have been accomplished using flexible devices such as endoscopes,balloons, snares and electrosurgical tools well known in the art.

While many of these devices and techniques have been useful inidentifying and removing some neoplastic lesions of the mucosal layer aswell as providing access to general locations within the digestive tractfor the placement of submucosal implants, there are some lesions andareas of the digestive tract which are extremely difficult to resect oraccess. For example, the en bloc removal of large flat mucosal lesionspresents numerous problems for current endoscopic tools and techniques.In addition, to effectively diagnosis some disorders (gastric motility,irritable bowel syndrome, chronic intestinal pseudo-obstruction, etc.) abiopsy of the muscular wall or the myenteric plexus may be necessary.Currently, access to these types of specimens requires full thicknessbiopsies which can be particularly difficult from an endoscopic approachrequiring extremely skilled closure techniques.

There have been some advances in endoscopic techniques to resect flatlesions of the mucosal layer generally termed, Endoscopic MucosalResection (EMR). One of these EMR techniques, “lift and cut”, involvesthe injection of saline or other biocompatible solution beneath thelesion in an attempt to raise the lesion thereby changing the geometryto make it suitable for resection using conventional snare devices.

Modifications to this technique are disclosed in U.S. Pat. No. 5,651,788in which a lesion is identified and an injection catheter is used toinject saline to elevate the lesion. A ligator is attached to the distalend of the endoscope and suction is applied to the lesion to bring thetissue into the ligator. A ligator band is then applied to the tissue toform a banded mushroom-like polyp which is suitable for removal with anelectrosurgical snare.

Alternatively U.S. Pat. No. 5,961,526 discloses a coaxial needle andsevering snare assembly in which a needle is used to pierce tissueadjacent a target lesion to elevate the lesion with saline. Once thelesion is elevated, the needle is retracted from the tissue and thesnare is extended from the needle lumen to surround the lesion. Thelesion is then aspirated into an aspiration cylinder adjacent the distalend of the endoscope and the snare is cinched to sever the tissuesurrounding the lesion.

While EMR techniques have been shown to be effective in treating someflat neoplastic lesions there are limitations and complicationsassociated with these techniques. A major limitation associated withthis technique is the size of the lesion that can be resected.Generally, these EMR techniques are suitable only for resecting mucosallesions which are less than 2 cm in diameter. While larger or irregularshaped lesions may be resected in a piecemeal fashion, this isundesirable since small portions of the lesion may remain. Anotherlimitation of these techniques includes uncertainty of the area beingresected. Once tissue has been suctioned into a cap ligator oraspiration cylinder, the tissue is directly adjacent the visualizationmeans of the endoscope obscuring the field of view. One complicationassociated with these EMR techniques is in relation to the use of theneedle injection system. Manipulating the injection catheter to positionthe needle through the mucosal layer into the submucosal layer canultimately result in puncturing the muscular wall of the digestive tractwhich may lead to infection or peritonitis. Another complicationassociated with EMR techniques is damage to the underlying muscularlayer. Saline and other non-viscous fluids used to elevate the lesiondissipate relatively quickly after injection into the submucosal layer,such that portions of the underlying muscular layer may be included inthe suctioned tissue and inadvertently damaged when using theelectrosurgical tool for resection.

In order to overcome some of the size, irregular shapes andvisualization limitations associated with EMR techniques, a newprocedure called Endoscopic Submucosal Dissection (ESD) has beendeveloped. With this procedure the periphery of the target resectionarea, which includes the lesion, is marked. An injection catheter isused to deliver a viscous fluid within the submucosal layer, which doesnot readily dissipate, throughout the target resection area. Once thetarget resection area has been elevated, an incision is made through themucosal layer at the edge of the resection area using an electrosurgicalneedle knife. The physician uses the needle knife to cut the mucosallayer along the periphery of the target resection area. Once theboundary of the resection area has been cut, the physician then uses theneedle knife to manually cut the submucosal connective tissue bindingthe mucosal layer to the muscular wall. Once the physician has completedthe submucosal dissection, the mucosal layer is free to be removed inone piece. While this procedure allows the physician to resect large,irregular shaped lesions en bloc, it requires a high degree of skill onthe part of the physician and is still subject to the complicationsassociated with needle perforations and muscular layer injury.

In performing the ESD method of resecting a neoplastic lesion, as wellas, performing a submucosal medical procedure it is apparent thatdissecting the connective tissue of the submucosal space is an importantstep in having a successful outcome. Numerous investigators haveattempted to provide ways of dissecting the submucosal connectivetissue.

In U.S. Pat. No. 6,098,629 a method of implanting a submucosalesophageal bulking device is disclosed. The patent further discloses theuse of a blunt dissecting member to create a submucosal pocket. Inaddition, the patent discloses the use of a balloon inserted into thesubmucosal layer to dissect the submucosal tissue when dilated to form asubmucosal pocket.

In PCT Patent Application No. WO 02/089655, methods of implantingsubmucosal gastric implants are disclosed. The application furtherdiscloses various configurations of mechanical and electrosurgicaldissection instruments for dissecting the connective tissue of thesubmucosal layer to form a submucosal pocket in which to place a gastricimplant. Included in the description of mechanical dissectioninstruments are various configurations of balloon dissectioninstruments.

In U.S. Patent Application No. US2005/0149099, a submucosal dissectioninstrument, system and method are disclosed. The application furtherdiscloses an electrosurgical high frequency knife in combination with asubmucosal dissection balloon. Included in the method are the steps ofsequentially activating the high frequency knife to create a hole andadvancing the balloon assembly into the hole with expansion of theballoon dissecting the connective tissue of the submucosal layer. Thesesteps of the method are repeated until all of the connective tissuebeneath the lesion is completely dissected.

With most of the aforementioned disclosed submucosal dissectiontechniques the physician is required to initially advance a significantportion of a dissection instrument into the submucosal layer while theconnective tissue is generally intact. These techniques require that apushing force be transmitted to the tip of the instrument to dissect thesubmucosal connective tissue. During application of this pushing forcethere is a risk that the tip of the instrument may injure or perforatethe muscular wall or the mucosal layer.

In performing the disclosed method using the electrosurgical highfrequency knife the initial hole through the mucosal layer may bevisualized endocopically. Once the balloon assembly is advanced into thesubmucosal incision hole and expanded to create a cavity, furtheradvancement of the high frequency knife to form a second hole must beconducted without visualization. During the second hole formation andsubsequent holes, without visual confirmation of the orientation of thehigh frequency knife there is a risk of perforating the muscular wall ormucosal layer.

SUMMARY OF THE INVENTION

In accordance with one aspect of the present invention there is provideda safe access needle injection instrument for use in a mammal. The safeaccess needle injection instrument includes an elongated flexibletubular member with proximal and distal ends and a lumen extendingtherethrough. A tissue holding member is positioned adjacent the distalend of the tubular member. A needle member having proximal and distalends with a lumen extending therethrough is slidably positioned withinthe lumen of the tubular member.

The tissue holding member is integrally formed with the tubular memberand is in the form of a window member adapted to engage the mucosaltissue within the digestive tract. A seal plug is included within thelumen of the tubular member distal to the window member. When a vacuumsource connected to the proximal end of the tubular member is activatedthe vacuum causes the mucosal tissue to be suctioned within the windowmember of the tissue holding member.

The needle member is coaxially disposed within the lumen of the tubularmember. The distal end of the needle member is operable from a firstposition proximal to the window member to a second position within thewindow member by axially advancing the needle member relative to thetubular member. Similarly, the distal end of the needle is operable froma second position within the window member to a first position proximalto the window member by axially retracting the needle member relative tothe tubular member. When a vacuum is applied to the tubular member, themucosal tissue is suctioned within the window member of the tissueholding member. The distal end of the needle member operated from itsfirst position to the second position to thereby pierce the mucosallayer of the tissue and enter the submucosal layer.

In accordance with another aspect of the present invention there isprovided a safe access needle injection instrument for use in a mammal.The safe access needle injection instrument includes an elongatedflexible tubular sheath member with proximal and distal ends and a lumenextending therethrough. A tissue holding member is positioned adjacentthe distal end of the tubular sheath member. A needle member havingproximal and distal ends with a lumen extending therethrough is slidablypositioned within the lumen of the tubular sheath member.

The tissue holding member takes the form of a pair of operable jawsconnected to the distal end of an elongate shaft member. The jaws areadapted to engage the mucosal tissue within the digestive tract. Theelongate shaft member is slidably disposed within the lumen of thetubular sheath member. The jaws are operable from an open configurationin which the jaws are biased outwardly when unconstrained, to a closedconfiguration in which the jaws approach each other when partially orfully constrained. When the tissue holding member is positioned adjacentthe distal end of the tubular sheath member and the jaws areunconstrained, proximal movement of the elongate shaft member relativeto the distal end of the tubular sheath, causes the jaws to be partiallyconstrained and move from the open configuration to the closedconfiguration.

The needle member is coaxially disposed within the lumen of the tubularmember. The distal end of the needle member is operable from a firstposition proximal to the tissue holding member jaws to a second positionbetween the tissue holding member jaws, by axially advancing the needlemember relative to the elongate shaft member. Similarly, the distal endof the needle is operable from a second position between the tissueholding member jaws to a first position proximal to the tissue holdingjaws by axially retracting the needle member relative to the elongateshaft member. When the jaws of the tissue holding member are positionedadjacent the mucosal tissue and are operated from an open to closedconfiguration, mucosal tissue is grasped and held between the jaws. Thedistal end of the needle member is then operated from the first positionto the second position to thereby pierced the mucosal layer of thetissue and enter the submucosal layer.

In accordance with another aspect of the present invention, the needlemember further includes a stop member positioned adjacent the distal endof the needle member. When the distal end of the needle member piercesthe mucosal layer, the stop member engages the mucosal tissue to therebylimit the depth to which the needle penetrates through the mucosallayer. Once the stop member engages the mucosal tissue it may also sealaround the needle such that fluid injected through the lumen of theneedle into the submucosal layer does not exit the puncture site of theneedle.

In accordance with a further aspect of the present invention, a methodis provided for operating a safe access needle instrument to create asafety bleb beneath the mucosal layer in the digestive tract of amammal. The method includes the step of providing a safe access needleinjection instrument. The safe access needle injection instrument havinga tubular member, tissue holding member and a needle member slidablydisposed within the lumen of the tubular member. The method alsoincludes the step of inserting the safe access needle injectioninstrument through a natural orifice into the digestive tract of amammal. The method additionally includes the step operating the safeaccess needle injection instrument to engage mucosal tissue with thetissue holding member. The method also includes the step of piercing themucosal layer with the needle member. The method further includes thestep of injecting fluid through the needle member into the submucosallayer.

In accordance with another aspect of the present invention there isprovided a safe access dissection system for use in a mammal. The safeaccess dissection system includes safe access needle injectioninstrument and an injectable dissection material. The injectabledissection material may take the form of a solution capable ofdissolving the submucosal connective tissue. An example of this type ofdissolving solution is sodium 2-mercaptoethanesulfanate (MESNA).Additional substances which may dissolve the submucosal connectivetissue include acids and enzymes such as a peptase enzyme solution,protease/collagenase, papain, chymotrypsin and acetylcycteine. Theinjectable dissection material may take the form of anon-pharmacological agent and provide a pure mechanical dissection ofthe submucosal tissue. The mechanical injectable dissection materialincludes injectable solutions which solidify upon entering thesubmucosal space, injectable semisolid gelatins, and injectable gelledmicrospheres. Solutions which solidify after injection into thesubmucosal space may be thermosensitive polymer solutions such asPluronic 127. Additional injectable solidifying solutions includemonomer and polymer solutions like hydrogels and cyanoacrylates whichpolymerize or crosslink upon contact with tissue or added chemicalagents. The semisolid gelatins and gelled microspheres may be formed ofnatural materials such as collagen and alginates or synthetic materialslike polyvinylalcohol (PVA), polyvinylpyrolidone (PVP) and acrylatepolymers.

In accordance with a further aspect of the present invention, a methodis provided for operating a safe access dissection system to create adissected safety bleb beneath the mucosal layer in the digestive tractof a mammal. The method includes the step of providing a safe accessneedle injection instrument and a dissecting material. The safe accessneedle injection instrument having a tubular member, tissue holdingmember and a needle member slidably disposed within the lumen of thetubular member. The method also includes the step of inserting the safeaccess needle injection instrument through a natural orifice into thedigestive tract of a mammal. The method additionally includes the stepoperating the safe access needle injection instrument to engage mucosaltissue with the tissue holding member. The method also includes the stepof piercing the mucosal layer with the needle member. The method furtherincludes the step of injecting a dissecting material through the needlemember into the submucosal layer where the submucosal connective tissueis dissected, separating the mucosal layer from the muscular layer. Themethod may additionally include the step of removing the dissectingmaterial from the mammal.

In accordance with an aspect of the present invention, there is provideda submucosal tunneling instrument. The submucosal tunneling instrumentincludes an elongate tubular member having proximal and distal ends anda lumen extending therethrough and an elongate expandable member locatedat the distal end of the tubular member. The expandable member hasproximal and distal ends wherein the proximal end of the expandablemember is connected to the distal end of the tubular member. Theexpandable member is everted, such that the distal end of the expandablemember is positioned within the lumen of the tubular member.

In accordance with an aspect of the present invention, there is provideda submucosal tunneling instrument. The submucosal tunneling instrumentincludes an elongate tubular member having proximal and distal ends anda lumen extending therethrough and an elongate expandable member locatedat the distal end of the tubular member. The expandable member hasproximal and distal ends wherein the proximal end of the expandablemember is connected to the distal end of the tubular member. Theexpandable member has a first spiral configuration, in which the distalend of the expandable member is positioned within center of the rolledspiral shape, and a second extended configuration in which the proximaland distal ends of the expandable member generally take the form of astraight line shape. The expandable member is operable from a firstspiral configuration to a second extended configuration. The expandablemember may also include a retaining member which maintains the shape ofthe expandable member in its first spiral configuration during deliveryand positioning of the submucosal tunneling instrument. The retainingmember may take the form of a spiral shaped coil member affixed to theballoon. The spiral shaped coil member may be formed from metals orpolymers which may be resilient or non-resilient.

In accordance with yet another aspect of the present invention, thesubmucosal tunneling instrument expandable member takes the form of aballoon. The balloon may be of the compliant or non-compliant typegenerally known in the art. The balloon may be formed from biocompatiblepolymer types such as olefins, elastomers, thermoplastic elastomers,vinyls, polyamides, polyimides, polyesters, fluropolymers, copolymersand blends of any of the aforementioned.

In accordance with still another aspect of the present invention, theexpandable member takes the form of a tubular framework. The tubularframework may be constructed in different fashions such as a laser cuttube, braided and non braided mesh tubes. The tubular framework may beformed from polymers such as olefins, thermoplastic elastomers, vinyls,polyamides, polyimides, polyesters, fluropolymers, copolymers and blendsof any of the aforementioned or metals such as stainless steel, nitinoland other biocompatible metallic alloys.

In accordance with another aspect of the present invention the distalend of the expandable member is connected to the distal end of a tethermember. The tether member is slidably disposed with the lumen of thetubular member and has a proximal end which is connected to a handlemember. The tether member takes the form of a flexible filament whichmay include a through lumen. The handle member may be used to adjust thelength of the tether member to thereby control the length of theexpandable member that is allowed to exit the lumen of the tubularmember.

In accordance with a further aspect of the present invention, a methodis provided for operating a submucosal tunneling instrument to create asubmucosal tunnel beneath the mucosal layer in the digestive tract of amammal. The method includes the step of creating a safety bleb beneaththe mucosal layer. The method also includes the step of providing asubmucosal tunneling instrument. The submucosal tunneling instrument hasan elongate tubular member, and an everted expandable member locatedwithin the distal lumen of the tubular member. The method also includesthe step of inserting the submucosal tunneling instrument through anatural orifice into the digestive tract of a mammal. The methodadditionally includes the step of forming an opening in the mucosallayer of the safety bleb. The method also includes the step ofpositioning the distal end of the submucosal tunneling instrumentthrough the formed opening in the mucosal layer. The method furtherincludes the step of operating the submucosal tunneling instrument tothereby extend and expand the expandable member from the tubular member,thereby forming a submucosal tunnel. The method then includes the stepof removing the submucosal tunneling instrument from the mammal.

In accordance with another aspect of the present invention there isprovided a submucosal tunneling system that includes a safe accessneedle injection instrument, a submucosal tunneling instrument. Thesubmucosal tunneling system may be provided in the form of a kit.

In accordance with still another aspect of the present invention thereis provided a submucosal dissecting instrument. The submucosaldissecting instrument includes an elongate tubular shaft member havingproximal and distal ends and a lumen extending therethrough and anexpandable member located at the distal end of the tubular shaft member.The submucosal dissecting instrument may further include a marker ormarkers spaced apart known distances on the shaft of the tubular memberto visually determine the length to which the distal end of the tubularmember has been inserted into a submucosal tunnel. The markers mayadditionally be made of radio-opaque material to thereby be visibleunder fluoroscopy.

In accordance with still yet another aspect of the present invention,the expandable member of the submucosal dissecting instrument takes theform of a balloon. The balloon may be of the compliant or non-complianttype generally known in the art. The balloon may be formed frombiocompatible polymer types such as olefins, elastomers, thermoplasticelastomers, vinyls, polyamides, polyimides, polyesters, fluoropolymers,copolymers and blends of any of the aforementioned.

In accordance with a further aspect of the present invention, a methodis provided for operating a submucosal dissecting instrument to create alarge mucosal layer dissected area in the digestive tract of a mammal.The method includes the step of forming an elongate submucosal tunnelbeneath the mucosal layer. The method also includes the step ofproviding a submucosal dissecting instrument. The submucosal dissectinginstrument has an elongate tubular member, and an expandable memberlocated at the distal end of the tubular member. The method alsoincludes the step of inserting the submucosal dissecting instrumentthrough a natural orifice into the digestive tract of a mammal. Themethod additionally includes the step of positioning the distal end ofthe submucosal dissecting instrument through an opening formed in themucosal layer into an elongate submucosal tunnel. The method furtherincludes the step of operating the submucosal dissecting instrument tothereby dilate the expandable member at the distal end of the tubularmember, thereby forming a large mucosal layer dissected area. The methodthen includes the step of removing the submucosal dissecting instrumentfrom the mammal.

In accordance with a further aspect of the present invention there isprovided a submucosal tunneling and dissecting instrument. Thesubmucosal tunneling and dissecting instrument includes an elongatefirst tubular member having proximal and distal ends and a lumenextending therethrough and an elongate first expandable member locatedat the distal end of the first tubular member. The first expandablemember has proximal and distal ends wherein the proximal end of thefirst expandable member is connected to the distal end of the firsttubular member. The first expandable member is everted, such that thedistal end of the first expandable member is positioned within the lumenof the first tubular member. The submucosal tunneling and dissectinginstrument also includes a second elongate tubular member havingproximal and distal ends and a lumen extending therethrough and a secondexpandable member located at the distal end of the second tubularmember. The elongate first tubular member is slidably disposed withinthe lumen of the elongate second tubular member, such that the distalend of the first tubular member may extend from the distal lumen of thesecond tubular member.

In accordance with another aspect of the present invention there isprovided a submucosal dissection system that includes a safe accessneedle injection instrument, a submucosal tunneling instrument and asubmucosal dissecting instrument. The submucosal dissection system maybe provided in the form of a kit. The submucosal dissection system mayinclude a submucosal tunneling instrument and a submucosal dissectinginstrument which are integrally formed.

In accordance with another aspect of the present invention there isprovided a submucosal implant device for diagnosing and treatingdisorders of the body. The submucosal implant device may be a passive oractive device. A passive submucosal implant device may take the form ofa drug delivery depot in which a therapeutic agent within the depotelutes from the depot according to a predetermined elution profile. Anactive submucosal implant device may take the form of a drug deliverydevice that incorporates a self contained diagnostic system to determinethe appropriate delivery time and dosage of a therapeutic agent to beadministered. The passive or active submucosal implant that takes theform of a drug delivery device may include a port positioned through themucosal layer to allow endoscopic refilling of the drug delivery devicewith therapeutic agents. The submucosal implant may include an anchormember in which to secure the implant to the muscular wall beneath themucosal layer.

In accordance with yet another aspect of the present invention there isprovided a method for performing a submucosal medical procedure todeploy a submucosal implant device in the digestive tract of a mammal.The method includes the step of forming a submucosal tunnel beneath themucosal layer in the digestive tract. The method also includes the stepof providing a submucosal implant device. The method includes the stepof inserting an endoscope through a mucosal opening into the areabeneath the mucosal layer. The method also includes the step ofpositioning a submucosal implant device in the area beneath the mucosallayer. The method additionally includes the step of releasing thesubmucosal implant device beneath the mucosal layer. The method alsoadditionally includes the step of closing the mucosal opening. Themethod then includes the step of removing the endoscope from the mammal.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view of an endoscope of a submucosal medical proceduresystem according to an embodiment of the present invention.

FIG. 2 is a side view of a safe access needle injection instrumentaccording to an embodiment of a submucosal medical procedure system ofthe present invention.

FIG. 3 is a partial cross-sectional view of a safe access needleinjection instrument according to an embodiment of a submucosal medicalprocedure system of the present invention.

FIG. 4 is a cross-sectional view taken along 4-4 of FIG. 3.

FIG. 5A is a partial cross-sectional view showing a first position ofthe needle of a safe access needle injection instrument according to anembodiment of a submucosal medical procedure system of the presentinvention.

FIG. 5B is a partial cross-sectional view showing a second position ofthe needle of a safe access needle injection instrument according to anembodiment of a submucosal medical procedure system of the presentinvention.

FIG. 6A through 6E are cross-sectional views showing a method creating asubmucosal bleb using the safe access needle injection instrument inaccordance with an embodiment of the present invention.

FIGS. 7A through 7C are partial cross-sectional views of a safe accessneedle injection instrument according to another embodiment of asubmucosal medical procedure system of the present invention.

FIGS. 8A through 8E are cross sectional views showing a method creatinga submucosal bleb using the safe access needle injection instrumentaccording to another embodiment of present invention.

FIG. 9 is partial cross-sectional view of a safe access needle injectioninstrument according to another embodiment of the present invention.

FIG. 10 is a perspective view of a safe access needle injectioninstrument according to another embodiment of the present invention.

FIGS. 11A and 11B are cross-sectional views showing a method fordissecting a submucosal layer according to an embodiment of the presentinvention.

FIGS. 12A and 12B are cross-sectional views showing a method fordissecting a submucosal layer according to another embodiment of thepresent invention.

FIGS. 13A and 13B are cross-sectional views showing a method fordissecting a submucosal layer according to yet another embodiment of thepresent invention.

FIG. 14 is a side view showing a submucosal tunneling instrument of asubmucosal medical procedure system in accordance with an embodiment ofthe present invention.

FIGS. 15A and B are a cross-sectional views showing a submucosaltunneling instrument of a submucosal medical procedure system inaccordance with an embodiment of the present invention.

FIGS. 16A through 16C are partial cross-sectional views showing asequence of expanding the distal end of a submucosal tunnelinginstrument of a submucosal medical procedure system in accordance withan embodiment of the present invention.

FIG. 17 is a side view showing a variation of a submucosal tunnelinginstrument of a submucosal medical procedure system in accordance withan embodiment of the present invention.

FIG. 18 is a cross-sectional view showing a sequence of expanding thedistal end of another variation a submucosal tunneling instrument of asubmucosal medical procedure system in accordance with an embodiment ofthe present invention.

FIGS. 19A through 19C are a side views showing another variation of asubmucosal tunneling instrument of a submucosal medical procedure systemin accordance with an embodiment of the present invention.

FIGS. 20A and 20B are perspective views showing a variation of thedistal end of a submucosal tunneling instrument of a submucosal medicalprocedure system in accordance with an embodiment of the presentinvention.

FIGS. 21A and 21B are perspective and cross sectional views of an areaof tissue in the digestive tract having a submucosal saline bleb inaccordance with an embodiment of the present invention.

FIGS. 22A and 22B are perspective and cross sectional views of an areaof tissue in the digestive tract having a submucosal saline bleb inwhich an opening through the mucosal layer is made in accordance with anembodiment of the present invention.

FIGS. 23A through 23D are perspective and cross sectional views showinga method of forming a submucosal tunnel using a submucosal tunnelinginstrument according to an embodiment of a submucosal medical proceduresystem of the present invention.

FIGS. 24A through 24D are perspective and cross sectional views showinga method of using a submucosal tunneling instrument according to anembodiment of a submucosal medical procedure system of the presentinvention.

FIGS. 25A through 25D are perspective and cross sectional views showinga method of using a submucosal dissection instrument in a submucosaltunnel according to an embodiment of a submucosal medical proceduresystem of the present invention.

FIG. 26 is a side view showing a combined submucosal tunneling anddissection instrument according to an embodiment of a submucosal medicalprocedure system of the present invention.

FIG. 27 is a broken cross-sectional view of a combined submucosaltunneling and dissection instrument according to an embodiment of asubmucosal medical procedure system of the present invention.

FIG. 28 is a cross-sectional view of the stomach showing a submucosalimplant according to an embodiment of a submucosal medical proceduresystem of the present invention.

FIGS. 29A through 29C are partial cross-sectional perspective viewsshowing a method of positioning a submucosal implant according to anembodiment of a submucosal medical procedure system of the presentinvention.

FIGS. 30A through 30C are partial cross-sectional perspective viewsshowing a method of positioning a submucosal implant according toanother embodiment of a submucosal medical procedure system of thepresent invention.

FIGS. 31A through 31F are partial cross-sectional perspective viewsshowing a method of delivering a submucosal implant to a desiredlocation within the digestive tract according to yet another embodimentof a submucosal medical procedure system of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Methods and devices for performing submucosal medical procedures in adesired area of the digestive tract using an endoscope are described.

FIG. 1 illustrates an endoscope 2 of the type used in endoscopicprocedures and suitable for use with embodiments of the presentinvention. The endoscope 2 has a working channel 4 extending from aproximal portion of the endoscope to the distal end of the endoscope.The endoscope 2 also has an insertion section 6 which enters the body ofa patient passing through a natural orifice such as the mouth or rectum.The insertion section 6 is generally navigated to a position with thedigestive tract when performing a submucosal medical procedure. Devicesfor use in performing submucosal medical procedures are preferablydelivered through working channel 4 of the endoscope 2; however devicesmay be delivered along side the insertion section 6 of the endoscope.

FIG. 2 illustrates a safe access needle injection instrument 10 which isused to aid the physician in obtaining access to the submucosal layer toperform a submucosal medical procedure. The safe access needle injectioninstrument 10 includes a tubular shaft 12 having a distal end 13. Thediameter of tubular shaft 12 is generally in the range 1 mm to 10 mmwith a preferred range of 2.0 to 6.0 mm. Adjacent distal end 13, aportion of the wall of tubular shaft 12 is removed to form window member14. Alternatively, window member 14 can be formed with a cap elementcoupled to the distal end of the tubular shaft 12. Slidably disposedwithin the lumen of tubular shaft 12 is needle member 16. The proximalportion of tubular shaft includes vacuum port 18 which is capable ofbeing coupled to a vacuum source such as a syringe or vacuum pump (notshown). Valve assembly 20 provides a releasable seal to tubular shaft12. A handle assembly 21 is connected to tubular shaft 12 throughconnector tubing 22. The handle assembly 21 includes needle fluid port24 and valve assembly 26 for injecting fluid through and sealing aroundthe proximal portion of needle member 16. The proximal portion of needlemember 16 is also connected to a needle slide member 28 positioned onhandle body 30. The proximal movement of needle slide member 28 onhandle body 30 causes needle member 16 to move proximally within tubularshaft 12. Distance markers 32 are located on handle body 30 to gauge themovement of needle member 16 within tubular shaft 12.

As shown in FIGS. 3 and 4, needle member 16 is positioned within lumen34 of tubular shaft 12. Located on the exterior of needle member 16 isstop member 36. The distal end 13 of tubular shaft 12 is closed withseal plug 38. Also shown is needle member tip 40 and needle lumen 42.Needle lumen 42 communicates needle tip 40 with needle fluid port 24 sothat fluid injected through needle port 24 exits the lumen at needle tip40.

FIGS. 5A and 5B, illustrate the actuation of needle member 16. Needlemember 16 is shown in detail with needle body 44 connected to needle tip40. Needle body 44 may be constructed of a separate material as shown orintegrally formed with needle tip 40. Needle body 44 may be constructedfrom flexible tubing having good axial pushability. As shown in FIG. 5A,needle member 16 is in a first position in which needle tip 40 islocated within lumen 34 proximal to window member 14. This is thepreferred position for needle member 16 when tubular shaft 12 isdeployed within the body. Upon actuation, needle member 16 is moved to asecond position in which needle tip 40 is positioned within windowmember 14.

FIGS. 6A through 6E illustrate the operation of safe access needleinjection instrument 10. Insertion section 6 of endoscope 2 is passedthrough a natural orifice in a patient and positioned at a location inthe digestive tract in which to perform a submucosal procedure. Safeaccess needle injection instrument 10 is deployed through the workingchannel 4 of endoscope 2. As depicted in FIG. 6A the distal potion ofsafe access needle injection instrument 10 is positioned within thedigestive tract adjacent mucosal layer 46. Beneath the mucosal layer arethe submucosal layer 48 and the muscular layer 50. Window member 14 isoriented towards mucosal layer 46. Needle member 16 is located in afirst position proximal to window member 14. A vacuum source isconnected to vacuum port 18, which communicates with lumen 34, and theapplied vacuum causes the tissue of the digestive tract to be suctionedinto window member 14 as shown in FIG. 6B. The actuation of needlemember 16 is shown in FIG. 6C as it is moved to its second position.Distal movement of needle member 16 causes needle tip 40 to movedistally relative to tubular shaft 12 to thereby pierce the mucosallayer 46 and enter the submucosal layer 48 of the suctioned tissue. Whenneedle member 16 is moved to its second position, stop member 36 engagesthe mucosal layer 46. Stop member 36 prevents further distal movement ofneedle member 16 and provides a seal around needle tip 40. A pressurizedfluid source is connected to needle fluid port 24 to deliver fluidthrough the lumen of needle member 16 to the submucosal layer 48. Asfluid enters the submucosal layer 48 from needle tip 40, as illustratedin FIG. 6D, the mucosal layer 46 is elevated forming a submucosal bleb.The fluid used to create the bleb may be of any type suitable for theenvironment such as solutions containing saline, hypertonic solutions ofsaline-epinephrine, sodium hyaluronate, poly-N-acetylglucosamine, sodiumchondroitin sulfate, chitosans or other biocompatiblemucopolysaccharides. Although the mucosal layer 46 is elevated to formthe submucosal bleb, the submucosal connective tissue 52 is onlystretched and not broken by the infusion of fluid into submucosal layer48. Once the needle member 16 is returned to its first position and theapplied vacuum to lumen 34 is discontinued, the safe access needleinjection instrument 10 may be removed from the safety bleb asillustrated in FIG. 6E.

FIGS. 7A through 7C illustrate safe access needle injection instrument60 which is another preferred embodiment of the present invention to aidthe physician in obtaining access to the submucosal space whenperforming a submucosal medical procedure. Safe access needle injectioninstrument 60 includes a sheath member 62 having a proximal and distalend 64 and a lumen 66 extending therethrough. Slidably disposed withinlumen 66 of sheath member 62, there is an elongate shaft member 68having a shaft lumen 69 and distal end 70. Located adjacent to distalend 70 of elongated shaft member 68 is a pair of jaw members 72. Jawmembers 72 may be formed from the wall of elongated shaft member 68.Preferably the jaw members 72 are formed of a resilient material andbiased outwardly in an open configuration when unconstrained. The jawmembers 72 may be formed from biocompatible resilient materials such asnitinol, stainless steel and plastics. Needle shaft 74 is slidablydisposed within lumen 66 and preferably slidably disposed shaft lumen69. Needle shaft 74 includes a needle tip 76 and a needle lumen 78.Needle lumen 78 extends from the proximal end of needle shaft 74 toneedle tip 76. FIG. 7A illustrates jaw members 72 in a first state inwhich jaw members 72 are closed and constrained by the walls of sheathmember 62 and disposed within lumen 66. Additionally, needle tip 78 ofneedle shaft 74 is in a first configuration in which needle tip 78 ispositioned proximal to jaw members 72. By moving the elongate shaftmember 68 distally relative to sheath member 62, jaw members 72 arecaused to exit the lumen 66 at distal end 64 of sheath 62. FIG. 7B showsjaw members 72 in a second state in which in which the jaw members 72are open and unconstrained after exiting lumen 66. FIG. 7C illustratesneedle tip 78 of needle shaft 74 positioned in a second configuration inwhich needle tip 78 is positioned between jaw members 72.

FIGS. 8A through 8E illustrates the operation of safe access needleinjection instrument 60. Insertion section 6 of endoscope 2 is passedthrough a natural orifice in a patient and positioned at a location inthe digestive tract in which to perform a submucosal procedure. Safeaccess needle injection instrument 60 is deployed through the workingchannel 4 of endoscope 2. As depicted in FIG. 8A the distal potion ofsafe access needle injection instrument 60 is positioned within thedigestive tract adjacent mucosal layer 46. Beneath the mucosal layer arethe submucosal layer 48 and the muscular layer 50. Jaw members 72 arepositioned on mucosal layer 46. Needle tip 76 is located in a firstposition proximal to jaw members 72. Distal movement of sheath member 62relative to the elongate shaft member causes the jaw members 72 tobecome partially constrained in lumen 66 and move towards a closedposition thereby grasping the tissue of the digestive tract as shown inFIG. 8B. FIG. 8C is a cross-section view along section line 8C-8C inFIG. 8B showing the tissue engaged by jaw members 72. The mucosal layer46 and submucosal layer 48 are firmly held between jaw members 72.Needle tip 76 is moved from the first position proximal to jaw members72 to the second position between jaw members 72 thereby piercing themucosal layer 46 and entering the submucosal layer 48 as shown in FIG.8D. FIG. 8E illustrates the delivery of fluid through needle shaft 74exiting needle tip 76 into the submucosal layer 48 thereby elevatingmucosal layer 46 to form a submucosal bleb. The fluid used to create thebleb may be of any type suitable for the environment such as solutionscontaining saline, hypertonic solutions of saline-epinephrine, sodiumhyaluronate, poly-N-acetylglucosamine, sodium chondroitin sulfate,chitosans or other biocompatible mucopolysaccharides.

FIGS. 9 and 10 show a variation of safe access needle injectioninstrument 60 in which jaw members 72 are coupled to distal end 70 ofelongate shaft member 68 by a collar member 80. Collar member 80 isjoined to distal end 70 by suitable means known in the art such asgluing, soldering or welding. Jaw members 72 are connected to collarmember 80 in a way that allows the jaw members 72 to rotate relative todistal end 70 of elongate shaft member 68. The rotational movement ofjaw members 72 allows the physician to quickly orient the jaw members 72relative the surface of the tissue surface within the digestive tract.Although jaw members 72 are connected to collar member 80, proximalmovement of elongate shaft member 68 relative to sheath member 62 willcause jaw members 72 to move to a closed position within the lumen 66 ofsheath member 62. Collar member 80 includes an aperture through whichneedle shaft 74 may extend in a slidable fashion. Additionally, jawmembers 72 include a tissue grasping surface 82 that facilitates theengagement of tissue within the digestive tract. While tissue graspingsurface 82 is shown in the form of a serrated surface, it may also takethe form of a knurled surface or a surface containing multipleprotrusions or dimples to improve the tissue grasping ability of jawmembers 72. Tissue grasping surface 82 may be integrally formed with jawmembers 72 or bonded to jaw members 72. Tissue grasping surface 82 maybe formed of metals, polymers or composite materials.

FIGS. 11A and 11B show a safe access dissection system 100 of thepresent invention that includes a safe access needle injectioninstrument 10 and an injectable dissection material 102. The injectabledissection material 102 takes the form of a solution capable ofdissolving the submucosal connective tissue. An example of this type ofdissolving solution is sodium 2-mercaptoethanesulfanate (MESNA).Additional substances which may dissolve the submucosal connectivetissue include acids and enzymes such as a peptase enzyme solution,protease/collagenase, papain, chymotrypsin and acetylcysteine. A safeaccess needle injection instrument 10 is used to create a safety blebbeneath the mucosal layer 46 in the digestive tract of a mammal. Oncethe safety bleb is formed, the injectable dissection material 102 may bedelivered through needle tip 40 into the submucosal layer 48 as shown inFIG. 11A. Injectable dissection material 102 begins to breakdown thestretched submucosal connective tissue 52. Under the force imparted bythe distention of the bleb, the submucosal connective tissue 52 breaks,thereby causing the mucosal layer 46 to be come detached from muscularlayer 50 in bleb region as shown in FIG. 11B.

FIGS. 12A and 12B show a safe access dissection system 104 of thepresent invention that includes a safe access needle injectioninstrument 10 and an injectable dissection material 106. The injectabledissection material 106 takes the form of a semisolid gelatin capable ofmechanically breaking the submucosal connective tissue 52. The semisolidgelatin may be formed using biocompatible commercially availablegelatins. Generally, these gelatins are in a powdered form and mixedwith warm water. Upon cooling, the gelatin forms a semisolid consistencywith physical cross links. The gelatin material is preferably formedwithin the barrel of a pressurizable syringe since aspiration of thismaterial is difficult. A safe access needle injection instrument 10 isused to create a safety bleb beneath the mucosal layer 46 in thedigestive tract of a mammal. Once the safety bleb is formed, theinjectable dissection material 106 may be delivered through needle tip40 into the submucosal layer 48 as shown in FIG. 12A. The mass andsemisolid nature of the injectable dissection material 106 begins toapply force to the stretched submucosal connective tissue 52, unlike asaline solution which only permeates the submucosal layer 48. Under theforce imparted by the increased volume due to the introduction of theinjectable dissection material 106, the submucosal connective tissue 52breaks, thereby causing the mucosal layer 46 to be come detached frommuscular layer 50 in bleb region as shown in FIG. 12B. Alternatively,the injectable dissection material 106 may also take the form ofinjectable solutions which solidify upon entering the submucosal space.Solutions which solidify after injection into the submucosal space maybe thermo sensitive polymer solutions such as Pluronic 127. Additionalinjectable solidifying solutions include monomer and polymer solutionslike hydrogels and cyanoacrylates which polymerize or crosslink uponcontact with tissue or added chemical agents.

FIGS. 13A and 13B show a safe access dissection system 108 of thepresent invention that includes a safe access needle injectioninstrument 10 and an injectable dissection material 110. The injectabledissection material 110 takes the form of gelled microspheres dispersedin a solution capable of mechanically breaking the submucosal connectivetissue 52. The microspheres may be formed using biocompatible naturalmaterials such as collagen and alginates or synthetic materials likepolyvinylalcohol (PVA), polyvinylpyrolidone (PVP) and acrylate polymers.A safe access needle injection instrument 10 is used to create a safetybleb beneath the mucosal layer 46 in the digestive tract of a mammal.Once the safety bleb is formed, the injectable dissection material 110may be delivered through needle tip 40 into the submucosal layer 48 asshown in FIG. 13A. The mass and solid nature of the injectabledissection material 110 begins to apply force to the stretchedsubmucosal connective tissue 52, unlike a saline solution which onlypermeates the submucosal layer 48. Under the force imparted by theincreased volume due to the introduction of the injectable dissectionmaterial 110, the submucosal connective tissue 52 breaks, therebycausing the mucosal layer 46 to become detached from muscular layer 50in bleb region as shown in FIG. 13B.

FIG. 14 illustrates a submucosal tunneling instrument 120 for performinga submucosal medical procedure of the present invention. The submucosaltunneling instrument 120 includes a catheter 122 having proximal anddistal ends and a balloon member 124 located adjacent the distal end.The proximal end of catheter 122 is attached to connector tubing 126 toaccess inflation port 128. Valve assembly 130 provides a seal for fluidintroduced into inflation port 128. Tether slide 132 is slidablypositioned on handle body 134. Handle body 134 includes distance markers136 to gauge the movement of tether slide 132.

A cross sectioned view of the distal end of the submucosal tunnelinginstrument 120 is shown in more detail in FIG. 15. Catheter 122 has adistal end 138 and a lumen 123. Located within lumen 123 is balloonmember 124. The balloon member 124 is preferably noncompliant of thetype generally known in the art, however, balloon member 124 may be ofthe compliant or semi-compliant type. The balloon member 124 may beformed from biocompatible polymer types such as olefins, elastomers,thermoplastic elastomers, vinyls, polyamides, polyimides, polyesters,fluropolymers, copolymers and blends of any of the aforementioned. Theproximal end 140 of balloon member 124 is attached to the distal end 138of catheter 122. The distal end 142 of balloon member 124 is positionedwithin the lumen 123 in an everted configuration. A tether member 144 isconnected to the distal end 142 of balloon member 124. Tether member 144is flexible and preferably takes the form of a filament, as shown,however tether member 144 may take the form of a tube. The proximal endof tether member 144 is connected to tether slide 132 through valveassembly 130. Tether member 144 aids in initially positioning balloonmember 124 within the lumen 123 of catheter 122. While theaforementioned embodiment of the submucosal tunneling instrument includean expandable member which preferably takes the form of an inflatableballoon, other devices may be suitable for essentially performing thesame function. For instance as depicted in an alternate embodiment shownin FIG. 15B, the expandable member 124 may take the form of anexpandable elongate braid, mesh or tubular framework in which theproximal end of the expandable member is connected to the distal end ofthe catheter and the distal end of the expandable member is everted andpositioned within the lumen of the catheter. A stiffened tether member144 located within the lumen of the catheter 122 may be used as a pusherto push the expandable elongate member from the lumen of the catheter inessentially the same way that the balloon expands from the lumen of thecatheter. The expandable elongate braid may be formed from resilientmaterials such as nitinol, spring steels, vitreloy, as well as polymersand composites. The expandable member may take comprise individual wiresto form a braid or mesh configuration. Alternatively the expandablemember may be laser cut from a tube forming a tubular framework.Preferably the expanded diameter is larger than the outer diameter ofthe catheter.

FIGS. 16A through 16C illustrate various stages of deployment of balloonmember 124 from the lumen 123 of catheter 122. To deploy balloon member124 a fluid filled syringe or other source is connected to inflationport 128. As pressurized fluid enters the lumen 123 of catheter 122, theproximal end of balloon member 124 exits the lumen expands. Balloonmember 124 has an expanded diameter range of about 1 mm to about 30 mmand is preferably in the range of 2 mm to 20 mm. The length of balloonmember 124 is a long as necessary to perform a desired submucosalmedical procedure. This length can be in the range of 5 mm to 50 cm andpreferably in the range of 7 mm to about 10 cm. As balloon member 124expands it extends in a linear fashion moving the distal end 142 ofballoon member 124 towards the distal end 138 of catheter 122. As longas pressurized fluid is applied to catheter lumen 123, balloon 124 willextend to its full length. Alternatively, since the distal end 142 ofballoon 124 is connected to tether member 144, the amount of linearextension balloon 124 takes may be controlled by the tether slide 132 todefine an extension length shorter than the full length of the balloon.

FIG. 17 illustrates a submucosal tunneling instrument 150 for performinga submucosal medical procedure of the present invention. The submucosaltunneling instrument 150 includes a catheter 152 having proximal anddistal ends and a balloon member 154 located adjacent the distal end.Positioned on the exterior of catheter 152 adjacent the distal end is aseries of markers 156. These markers may be visible under directvisualization of the endoscope and may be additionally visible underfluoroscopy. Adjacent the proximal end of catheter 152 is an auxiliarydevice port 158. The proximal end of catheter 152 is attached toconnector tubing 160 to access inflation port 162. Valve assembly 164provides a seal for fluid introduced into inflation port 162. Tetherslide 166 is slidably positioned on handle body 168. Handle body 168includes distance markers 170 to gauge the movement of tether slide 166.

A cross sectioned view of the distal end of the submucosal tunnelinginstrument 150 is shown in more detail in FIG. 18. Catheter 152 has adistal end 172 and a first lumen 174. Located within first lumen 174 isballoon member 154. The balloon member 154 is preferably non-compliantof the type generally known in the art, however, balloon member 154 maybe of the compliant or semi-compliant type. The balloon member 154 maybe formed from biocompatible polymer types such as olefins, elastomers,thermoplastic elastomers, vinyls, polyamides, polyimides, polyesters,fluropolymers, copolymers and blends of any of the aforementioned. Theproximal end 176 of balloon member 154 is attached to the distal end 172of catheter 152. The distal end 178 of balloon member 154 is positionedwithin the first lumen 174 in an everted configuration. A tether member180 is connected to the distal end 178 of balloon member 154. Tethermember 180 is flexible and preferably takes the form of a filament, asshown, however tether member 180 may take the form of a tube. Theproximal end of tether member 180 is connected to tether slide 166through valve assembly 164. Tether member 180 aids in initiallypositioning balloon member 154 within the first lumen 174 of catheter152. Catheter 152 has a second lumen 182 that extends from auxiliarydevice port 158 to distal end 184. Distal end 184 is located proximal todistal end 172 of catheter 152. Slidably disposed within second lumen182 is a needle knife 184 that has a knife tip 188. Needle knife 184 ispreferably of the endoscopic electrosurgical type however any form ofincision device that may be operated to form an incision in tissue suchas mechanical cutters, water jets or lasers may be suitable.

FIGS. 19A through 19C illustrate a submucosal tunneling instrument 200,according to another embodiment of the present invention. Catheter 202has a distal end 204 which is connected to balloon member 206. Theproximal end 208 of balloon 206 is connected to distal end 204 ofcatheter 202. Balloon member 206 is rolled into a spiral configurationin which the distal end 210 is located in the center of the spiral. Asthe lumen of catheter 202 which is connected to balloon member 206 ispressurized, balloon member 206 inflates. The inflation of balloonmember 206 causes the balloon to unroll from a spiral configurationextending linearly. The balloon member 206 may be thermally treated toretain the spiral configuration for delivery through the working channelof an endoscope. Alternatively the balloon member 206 may incorporate aspiral shaped member 212 attached the wall of balloon member 206 asshown in FIGS. 20A and 20B. The spiral shaped member may be formed froma resilient filament as shown in an outstretched configuration in FIG.20A. The spiral shaped member being formed of a resilient filament andincorporated into the wall of the balloon preferably takes its spiralshape and in doing so forms the balloon member into a spiral shape asshown in FIG. 20B.

In order to perform a submucosal medical procedure, the target area inthe digestive tract must be prepared to gain access to the submucosalspace. FIGS. 21A and 21B illustrate a desired region 220 of thedigestive tract of a mammal. A safe access needle injection instrumentaccording to any of the embodiments previously described may be used toform a safety bleb 222 beneath the mucosal layer 46. The safety blebcontains the submucosal connective tissue 52 generally in a stretchedcondition attached to both the mucosal layer 46 and the muscular layer50. As shown in FIGS. 22A and 22B, an endoscopic incision tool 224 ispositioned adjacent to the safety bleb 222. An incision tool tip 226 ofthe endoscopic incision tool 224 is used to create a small mucosalopening 228 in the mucosal layer 46 of the safety bleb. The elevatedmucosal layer 46 reduces the likelihood that the incision tool tip 226will damage the underlying muscular layer 50. FIGS. 23A through 24Dillustrate the introduction and operation of a submucosal tunnelinginstrument into submucosal layer 48. The distal end 138 of thesubmucosal tunneling instrument 120 is positioned through the mucosalopening 228. Once the proximal end 140 of balloon 124 is through themucosal opening 228 the submucosal tunneling instrument 120 may beoperated. By delivering pressurized fluid through the lumen of catheter122, the proximal end 140 of balloon 124 inflates to its expandeddiameter as depicted in FIG. 23C. Generally the expanded diameter of theproximal end 140 of balloon 124 is larger than the diameter of themucosal opening 228. The larger diameter prevents balloon 124 frompushing the distal end 138 of catheter 122 backwards out of thesubmucosal layer 48 through mucosal opening 228. As shown in FIG. 23D,further inflation extends balloon 124 in a linear fashion within thesubmucosal layer 48 causing the submucosal connective tissue 52 to breakin regions adjacent to the balloon. The balloon 124 can only expand byincreasing the volume of the surrounding area between the mucosal layer46 and the muscular layer 50. The application of force during expansionof balloon 124 is concentrated on the submucosal connective tissue 52,thereby causing the submucosal connective tissue 52 to break, whereasthe force applied to the mucosal layer 46 or the muscular layer 50 byballoon 124 is diluted over a larger portion of balloon 124. The forcerequired to break the submucosal connective tissue 52 as applied byballoon 124 is less than the force required to perforate the mucosallayer 46 or muscular layer 50 by balloon 124 thereby minimizing traumato surrounding tissue. FIG. 24A illustrates a perspective view of region220 in the digestive tract having a submucosal tunnel 230 formed bysubmucosal tunneling instrument 120. As shown in FIG. 24B, balloon 124is fully expanded and generally occupies the majority of the space ofsubmucosal tunnel 230. Balloon 124 is then deflated by applying anegative pressure to catheter 122 and retracting tether member 144. Thedistal end 138 of catheter 122 is then removed from mucosal opening 228,leaving submucosal tunnel 230 generally deflated. The submucosalconnective tissue 52 within the tunnel is broken. For some submucosalmedical procedures the submucosal tunnel 230 may provide suitable accessto the muscular wall or the placement of an implant device. However toperform other submucosal medical procedures an area larger than thesubmucosal tunnel 230 may be desired.

FIGS. 25A through 25D illustrate the formation of an area larger than asubmucosal tunnel for performing a submucosal medical procedureaccording to an embodiment of the present invention. A region 220 in thedigestive tract is prepared by forming a submucosal tunnel 230. Asubmucosal dissection instrument 240 having a catheter 242 is positionedthrough mucosal opening 228 into submucosal tunnel 230. Located oncatheter 242 are markers 244 that indicate the insertion depth ofcatheter distal end 246 within submucosal tunnel 230. The submucosaldissection instrument 240 is in a proper position for operation whenballoon member 248 including distal end 250 and proximal end 252 aresufficiently located within submucosal tunnel 230, as shown in FIG. 25B.As pressurized fluid is applied to a lumen in catheter 242 that is influid communication with balloon member 248, balloon member 248inflates. During the expansion of balloon member 248, the submucosalconnective tissue 52 is broken in the area of the expanded balloonmember 248 and the mucosal layer 46 is elevated. The elevated mucosallayer 46 forms a large mucosal dissected area 260. After full expansionthe balloon member 248 may be deflated and submucosal dissectinginstrument 240 removed from the large mucosal dissected area 260. Thedissected region beneath mucosal layer 46 has transformed in geometryfrom a high aspect ratio tunnel to a low aspect ratio chamber suitablefor performing some submucosal medical procedures.

Aforementioned descriptions of submucosal tunneling instruments andsubmucosal dissecting instruments have shown separate instruments tocreate a submucosal tunnel or large mucosal dissected area however thetwo types of instruments may be combined to form a submucosal tunnelingdissecting instrument 270 as illustrated in FIG. 26. The submucosaltunneling dissecting instrument 270 includes a dissection catheter 272having a distal end 274 and a dissection balloon 276 having an expandeddissection balloon 276 a configuration. The dissection balloon 276 canbe compliant of the type generally known in the art or dissectionballoon 276 may be of the compliant or semi-compliant type. Thedissection balloon 276 may be formed from biocompatible polymer typessuch as olefins, elastomers, thermoplastic elastomers, vinyls,polyamides, polyimides, polyesters, fluropolymers, copolymers and blendsof any of the aforementioned. The dissection catheter 272 has insertionmarkers 278 positioned along its shaft. The proximal end of dissectioncatheter 272 includes both an inflation port 280 that is in fluidcommunication with dissection balloon 276, and a valve assembly 282.Tunneling catheter 284 is slidably disposed through valve assembly 282extending within a lumen of dissection catheter 272. The tunnelingcatheter distal end 286 may extend beyond the dissection catheter distalend 274. Tunneling catheter 284 includes an inflation port 288 and valveassembly 290. A tether slide member 292 is slidably disposed on handlebody 294 with distance markers 296. FIG. 27 illustrates a detailed crosssection of the distal portion of the submucosal tunneling dissectinginstrument 270. The distal end 298 and proximal end 300 of dissectionballoon 276 are connected to the exterior of dissection catheter 272.Inflation lumen 302 connects inflation port 280 with the interior ofdissection balloon 276 through inflation aperture 304. Tunnelingcatheter 284 is slidably disposed within the lumen 306 of dissectioncatheter 272. Positioned within the lumen 308 of tunneling catheter 284there is an everted expandable tunneling balloon 310. The tunnelingballoon 310 is preferably non-compliant of the type generally known inthe art, however, tunneling balloon 310 may be of the compliant orsemi-compliant type. The tunneling balloon 310 may be formed frombiocompatible polymer types such as olefins, elastomers, thermoplasticelastomers, vinyls, polyamides, polyimides, polyesters, fluropolymers,copolymers and blends of any of the aforementioned. The distal end oftunneling balloon 310 is connected to a tether member 312 which has aproximal end that is connected to tether slide 292.

The operation of the submucosal tunneling dissecting instrument 270 toform a submucosal tunnel and large mucosal dissected area is similar tothe operation of the separate instruments. In general, the distal end286 of tunneling catheter 284 is positioned through a mucosal openingformed in a safety bleb. The tunneling catheter 284 is pressurized withfluid to linearly expand tunneling balloon 310. Once a submucosal tunnelhas been formed tunneling balloon 310 may be deflated and dissectioncatheter 272 may be advanced through the mucosal opening into thesubmucosal tunnel. The markers 278 may be used to determine the depth inwhich the dissection catheter 272 has been advanced into the submucosaltunnel. Once the dissection catheter 272 has been properly positionedwithin the submucosal tunnel it may be operated. By applying pressurizedfluid to inflation port 280, dissection balloon 276 is dilated to anexpanded dissection balloon 276 a configuration. During the expansion alarge mucosal dissected area is created which is accessible forperforming a subsequent submucosal medical procedure.

Another embodiment of the present invention includes a submucosalimplant device for diagnosing and treating disorders of the body. Thesubmucosal implant device may be a passive or active device. Activedevices may include self contained electronics for controlling thedevice, as well as an internal power supply. Alternatively, the activedevices may be controlled externally by telemetry. A passive submucosalimplant device may take the form of a drug delivery depot in which atherapeutic agent within the depot elutes from the depot according to apredetermined elution profile. An active submucosal implant device maytake the form of a drug delivery device that incorporates a selfcontained diagnostic system to determine the appropriate delivery timeand dosage of a therapeutic agent to be administered. The passive oractive submucosal implant device which takes the form of a drug deliverydevice may include a port positioned through the mucosal layer to allowendoscopic refilling of the drug delivery device with therapeuticagents. Submucosal implant devices that are drug delivery devices havethe ability to deliver therapeutic agents directly to the portalcirculation. Many different types of therapeutic agents may be deliveredsuch as pharmaceuticals, hormones, growth factors and other biologicalcompounds. Some typical therapeutic agents for use in a submucosalimplant device of the present invention include dromostanolone,dromostanolone propionate, chlormadinone, chlormadinone acetate,dimethisterone, ethisterone, hydroxyprogesterone, norgestomet and othernorsteroids such as norethindrone, norgesterone, northylodrel,norgestrel, noregestrienone, and norgestoniel; melengestrol acetate,estradiol, 17α-acetoxy-11β-methyl-19-norpregn-4-ene-3,20-dione,3(3-oxo-11β,13β-dialkl-17β-hydroxygon-4-en-17α-yl)propionicacid-lactone, 3-(3-oxo-11βmethyl-17β-hydroxyestr-4-en-17α-yl)-propionicacid lactone, 11,13β-dialkyl-17 lower alkyl-17 lower alkyl-gon-4-en-3one, 19-norpregn-4-ene-3,20-dione, oxytocin, vasopressin,adrenocorticotropic hormone, epidermal growth factor, prolactin,luliberin, luteinizing hormone releasing factor, growth hormonereleasing factor, insulin, somatostatin, glucagon, interferon, gastrin,tetragastrin, pentagastrin, urogestrone, secretin, calcitonin,enkephalins, endorphins, angiotensins, renin, bradykinin, bacitracins,polymyxins, colistins, tyrocidin, gramicidines, synthetic analogues,modifications and pharmaceutically-active fragments of polypeptides,monoclonal antibodies, soluble vaccines, somatropin, somatotropin,cosyntropin, gonadotropins, chorionic gonadotropin, thyrotropinreleasing hormone, thyroid stimulating hormone, pancreozymin andenkephalins.

By delivering therapeutics submucosally, some problems, such asdigestion, which prevent the oral delivery of some therapeuticcompounds, may be overcome. One such therapeutic compound that may bedelivered through the submucosal implant device that cannot beadministered orally is the hormone cholecytokinin (CCK). This hormonehas been shown to be instrumental in triggering the brain to tell thebody to stop eating by inducing satiety. As an appetite suppressant thiscompound may aid in the treatment of obesity.

An active submucosal implant device may take the form of a drug deliverydevice in which electrical signals are received from the contraction ofthe muscular wall of a mammal to deliver a specified amount oftherapeutic agent. The submucosal implant may include an anchor memberin which to secure the implant to the muscular wall beneath the mucosallayer. This anchor may be integrally formed with an electrode forreceiving electrical signals from the wall. Multiple submucosal implantdevices may be deposited at various locations along the stomach wall.

FIG. 28 shows a portion 409 of the digestive system in which asubmucosal implant device 410 is placed within the wall of the stomach.FIGS. 29A through 29C illustrate a sequence for deploying a submucosalimplant device according to an embodiment of the present invention. Asubmucosal tunnel 230 or a large mucosal dissected area is formed in aportion of the digestive tract. The insertion section 6 of an endoscopeis positioned through an enlarged mucosal opening 228 into thesubmucosal space. The submucosal implant device 410 and an implantdeployment device 412 are inserted through the mucosal opening 228 andpreferably through a working channel of the endoscope into thesubmucosal space. Implant deployment device 412 is used to positionsubmucosal implant device 410 within the submucosal space. Submucosalimplant device 410 preferably takes the form of a drug delivery depot.The submucosal implant device may be in the form of a hydrogel, gelmatrix, soluble wax or configurations commonly used in transdermal drugdelivery devices. Submucosal implant device 410 is shown in a firstconfiguration for delivery into the submucosal space and a secondconfiguration for deployment adjacent muscular layer 50. Implantdeployment device 412 is operated to move submucosal implant device 410from its first configuration to the second configuration. Implantdeployment device 412 then releases submucosal implant device 410 intothe submucosal space. The implant deployment device 412 and endoscopeinsertion section 6 are then removed from the submucosal space and themucosal opening 228 is then closed using clips, suture or other closuretechniques.

FIGS. 30A through 30C illustrate a submucosal implant device andsequence for deploying the device according to another embodiment of thepresent invention. A submucosal tunnel 230 or a large mucosal dissectedarea is formed in a portion of the digestive tract. The insertionsection 6 of an endoscope is positioned through an enlarged mucosalopening 228 into the submucosal space. The submucosal implant device 414and an implant deployment device 416 are inserted through the mucosalopening 228 and preferably through a working channel of the endoscopeinto the submucosal space. The relative sizes shown are for clarity; inpractice, implant device be relatively smaller to permit passage throughthe working channel Implant deployment device 416 is used to positionsubmucosal implant device 414 within the submucosal space. Submucosalimplant device 414 also includes an anchor member 418 and a tethermember 420. Anchor member 418 is adapted to be affixed to the muscularlayer 50 and retain the submucosal implant device 414 in position bytether member 420. Submucosal implant device 414 preferably takes theform of a drug delivery device. In addition to performing anchoring andtethering functions, anchor member 418 and tether member 420 alsofunction as an electrode and electrical conductor respectively.Electrical signals may be received by the submucosal implant device 414from muscular layer 50 via anchor member 418 and tether member 420.Implant deployment device 416 then releases submucosal implant device414 into the submucosal space. The implant deployment device 416 andendoscope insertion section 6 are then removed from the submucosal spaceand the mucosal opening 228 is then closed using closure clips 422 witha clip applier 424. Other closure techniques and devices such assutures, staples and adhesives may also be suitable for closing mucosalopening 228.

FIGS. 31A through 31F illustrate another submucosal implant device and asequence for deploying the device according to another embodiment of thepresent invention. A submucosal tunnel 230 or a large mucosal dissectedarea is formed in a portion of the digestive tract. The insertionsection 6 of an endoscope is positioned through an enlarged mucosalopening 228 into the submucosal space. The submucosal implant device 430and an implant deployment device 432 are inserted through the mucosalopening 228 and preferably through a working channel of the endoscopeinto the submucosal space. The relative sizes shown are for clarity; inpractice, implant device be relatively smaller to permit passage throughthe working channel. Implant deployment device 432 is used to positionsubmucosal implant device 430 within the submucosal space. Submucosalimplant device 430 includes a therapeutic agent delivery port 434, ananchor member 436 and a tether member 438. Anchor member 436 is adaptedto be affixed to the muscular layer 50 and retain the submucosal implantdevice 430 in position by tether member 438. Submucosal implant device430 preferably takes the form of a therapeutic drug delivery deviceincorporating an internal drug reservoir. In addition to performinganchoring and tethering functions, anchor member 436 and tether member438 also function as an electrode and electrical conductor respectively.Electrical signals may be sent and received by the submucosal implantdevice 430 to and from muscular layer 50 via anchor member 436 andtether member 438. The electrical signals may be used by the submucosalimplant device 430 to initiate or terminate delivery of a therapeuticagent through delivery ports 434. Submucosal implant device 430 alsoincludes a refill tube 440 connected to a mucosal port 442. Mucosal port442 contains a valve assembly that can restrict fluid access to refilltube 440. Implant deployment device 432 positions the refill tube 440within the submucosal space while the mucosal port 442 is positionedthrough mucosal layer 46. Implant deployment device 432 then releasessubmucosal implant device 430 into the submucosal space. The implantdeployment device 432 and endoscope insertion section 6 are then removedfrom the submucosal space and the mucosal opening 228 is then closedusing closure clips 422 with a clip applier 424. Other closuretechniques and devices such as sutures, staples and adhesives may alsobe suitable for closing mucosal opening 228. The endoscope and relatedmaterials may then be removed from the patient. At a later time period,after the reservoir of submucosal implant device 430 has been depletedthe physician may return endocopically to the site of the implant anduse a refilling instrument 444 having a tip 446 that engages the mucosalport 442 to deliver more drugs to refill the reservoir.

Novel instruments, systems and methods have been disclosed to performsubmucosal medical procedures in the digestive tract of a mammal.Although preferred embodiments of the invention have been described, itshould be understood that various modifications including thesubstitution of elements or components which perform substantially thesame function in the same way to achieve substantially the same resultmay be made by those skilled in the art without departing from the scopeof the claims which follow.

1. A submucosal implant system comprising: a safe access needleinjection means having a needle member adapted to pierce a mucosaltissue and deliver fluid to a submucosal layer; a submucosal tunnelingmeans; a submucosal dissection means; and, an implantable therapeuticagent delivery device.
 2. A submucosal implant system according to claim1 wherein said safe access needle injection means comprises: an elongatetubular member having proximal and distal ends and a lumen extendingtherethrough; a tissue holding member positioned adjacent the distal endof said elongate tubular member and is adapted to engage a desiredregion of a mucosal layer; and, said needle member having a lumenwherein said needle member is slidably disposed within the lumen of saidelongate tubular member and adapted to pierce a desired region of themucosal layer engaged by said tissue holding member and enter thesubmucosal layer such that delivery of a fluid through the lumen of saidneedle member enters said submucosal layer to thereby elevate saiddesired region of the mucosal layer.
 3. A submucosal implant systemaccording to claim 1 wherein said submucosal tunneling means comprises:an elongate tubular member having proximal and distal ends and a lumenextending therethrough; and, an expandable member having proximal anddistal ends wherein the proximal end of said expandable member isattached to the distal end of said tubular member and the distal end ofsaid expandable member is everted and positioned within the lumen ofsaid tubular member, wherein the distal end of said elongate tubularmember is adapted to enter an opening through the mucosal layer and intothe submucosal layer of a mammal.
 4. A submucosal implant systemaccording to claim 1 wherein said submucosal dissecting means comprisesan elongate tubular member having proximal and distal sections and anexpandable member disposed at the distal section of said tubular member.5. A submucosal implant system according to claim 3 wherein saidsubmucosal dissecting means comprises an elongate tubular member havingproximal and distal sections and an expandable member disposed at thedistal section of said tubular member.
 6. A submucosal implant systemaccording to claim 5 wherein said submucosal tunneling means and saidsubmucosal dissecting means are integrally formed.
 7. A submucosalimplant system, comprising: a safe access needle injection means havinga needle member adapted to pierce mucosal tissue and deliver fluid tothe submucosal layer; a submucosal tunneling means; a submucosaldissection means; and, an implantable drug delivery device.
 8. Asubmucosal implant system according to claim 7 wherein said safe accessneedle injection means comprises: an elongate tubular member havingproximal and distal ends and a lumen extending therethrough; a tissueholding member positioned adjacent the distal end of said elongatetubular member and is adapted to engage a desired region of a mucosallayer; and, said needle member having a lumen wherein said needle memberis slidably disposed within the lumen of said elongate tubular memberand adapted to pierce a desired region of the mucosal layer engaged bysaid tissue holding member and enter the submucosal layer such thatdelivery of a fluid through the lumen of said needle member enters saidsubmucosal layer to thereby elevate said desired region of the mucosallayer.
 9. A submucosal implant system according to claim 7 wherein saidsubmucosal tunneling means comprises: an elongate tubular member havingproximal and distal ends and a lumen extending therethrough; and, anexpandable member having proximal and distal ends wherein the proximalend of said expandable member is attached to the distal end of saidtubular member and the distal end of said expandable member is evertedand positioned within the lumen of said tubular member, wherein thedistal end of said elongate tubular member is adapted to enter anopening through the mucosal layer and into the submucosal layer of amammal.
 10. A submucosal implant system according to claim 7 whereinsaid submucosal dissecting means comprises an elongate tubular memberhaving proximal and distal sections and an expandable member disposed atthe distal section of said tubular member.
 11. A submucosal implantsystem, comprising: a safe access needle injection means having a needlemember adapted to pierce mucosal tissue and deliver fluid to thesubmucosal layer; a submucosal tunneling means; and, an implantable drugdelivery device.
 12. A submucosal implant system according to claim 11wherein said safe access needle injection means comprises: an elongatetubular member having proximal and distal ends and a lumen extendingtherethrough; a tissue holding member positioned adjacent the distal endof said elongate tubular member and is adapted to engage a desiredregion of a mucosal layer; and, said needle member having a lumenwherein said needle member is slidably disposed within the lumen of saidelongate tubular member and adapted to pierce a desired region of themucosal layer engaged by said tissue holding member and enter thesubmucosal layer such that delivery of a fluid through the lumen of saidneedle member enters said submucosal layer to thereby elevate saiddesired region of the mucosal layer.
 13. A submucosal implant systemaccording to claim 11 wherein said submucosal tunneling means comprises:an elongate tubular member having proximal and distal ends and a lumenextending therethrough; and, an expandable member having proximal anddistal ends wherein the proximal end of said expandable member isattached to the distal end of said tubular member and the distal end ofsaid expandable member is everted and positioned within the lumen ofsaid tubular member, wherein the distal end of said elongate tubularmember is adapted to enter an opening through the mucosal layer and intothe submucosal layer of a mammal.
 14. A submucosal implant systemaccording to claim 11 wherein said implantable drug delivery deviceincludes an anchor.
 15. A submucosal implant system according to claim12 wherein said implantable drug delivery device includes an anchor. 16.A submucosal implant system according to claim 13 wherein saidimplantable drug delivery device includes an anchor. 17.-42. (canceled)43.-52. (canceled)